1. KINS 7338 Micronutrient Metabolism in Sports Nutrition Pantothenic Acid Alaine Mills

2. History Pantothenic Acid was first isolated in 1931 by R.J. Williams Structure was determined in 1939 Essentially was not discovered, however, until 1954. Also known as “Pantothenate” The vitamin was once called vitamin B 5

3. Structure Consists of: β- Alanine Pantoic Acid Joined by a peptide bond/amide linkage *See structure (figure 9.17) on page 339 Commonly found bound to Coenzyme A Structure (figure 9.18) on page 340

4. Chemistry & Activity Pantothenic acid is not considered very stable Easily destroyed by heat Cooking Destroyed in acidic or alkaline conditions Stable in a neutral solution only In supplements it is usually included as calcium pantothenate More stable

5. Body Distribution Pantothenic acid along with 4’-phosphopantothenate and pantetheine may be found in the body’s cells Free Pantothenic acid is found in plasma, however, higher concentrations are found intracellularly Mainly in RBC’s Most ingested pantothenic acid is used to synthesize or resynthesize CoA Found in fairly high concentrations in the Liver Adrenal gland Kidney Brain Heart

6. Biomechanical Mechanism Functions in the body as a component of CoA and 4’- phosphopantetheine The synthesis of these from pantothenic acid requires pantothenic acid, the amino acid cysteine, and ATP Steps Pantothenic acid → 4’- phosphopantetheine Via pantothenate kinase ATP and Mg2+ required To form Coenzyme A from 4’- phosphopantetheine, a peptide bond is formed between the carboxyl group, and the amino group of cysteine Requires ATP

7. Biomechanical Mechanism The synthesis of CoA is inhibited by acetyl CoA, malonyl CoA, and propionyl CoA Pantothenic acid as 4’- phosphopantethine also functions as the prosthetic group for acyl carrier protein (ACP) Carriers or transporters of acetyl or acyl groups, as needed for various cellular reactions Forms Thio esters with carboxylic acid groups

8. Digestion, Absorption & Transport 85% of the pantothenic acid found in foods is bound to CoA. During digestion, CoA is hydrolyzed in the lumen to pantothenic acid Via phosphatases and pyrophosphatases Free pantothenic acid can then be absorbed (mainly in the jejunum) High concentrations by passive diffusion Low concentrations via a Na+ dependent active multivitamin transporter (SMVT) This carrier is also shared with biotin and lipoic acid

9. Digestion, Absorption & Transport 40 to 61% of pantothenic acid is absorbed From the intestinal cell, it will enter the portal blood for transport to body cells Pantothenic acid is found free in plasma, however, higher concentrations are found intracellularly, mainly in RBC’s Uptake by tissues Heart, liver, muscle, and brain Via Na+ dependent active transport Other tissues Via facilitated diffusion Most Pantothenic acid is used to synthesize or resynthesize CoA Found in fairly high concentrations in the liver, adrenal gland, kidney, brain, and heart

10. Functions Functions in the body as a component of CoA and 4’- phosphopantetheine. As a part of these, pantothenic acid participates extensively in nutrient metabolism Degredation rxns resulting in energy production Synthetic reactions for the production of many compounds Thus, it is important for the maintenance and repair of all cells and tissues CoA also acetylates (donation of the long chain-fatty acids or acetate) nutrients including sugars and proteins, and some drugs Acetylation of some enzymes results in either activation or inactivation

11. Functions The metabolism of CHO, lipids, and proteins relies on varying degrees of CoA. Ex: Pyruvate – Acetyl CoA Acetyl- CoA is the common compound formed from the three- energy producing nutrients Requires pantothenic acid Pantothenic acid joins the B vitamins thiamin, riboflavin, and niacin in the following: Decarboxylation of pyruvate Decarboxylation of α-ketoglutarate- Succinyl- CoA Used with Glycine to synthesize heme

12. Functions In lipid metabolism, CoA is important in the synthesis of Cholesterol Bile salts Ketone bodies Fatty Acids Steriod hormones

13. Functions Pantothenic acid as 4’- phosphopantetheine also functions as the prosthetic group for acyl carrier protein (ACP). Acts as the acyl carrier in the synthesis of fatty acids Is a necessary component of the fatty acid synthase complex The vitamin also appears to accelerate normal healing process following surgery Exact mechanism is still unclear

14. Excretion Does not appear to undergo metabolism prior to excretion Excreted intact in the urine Small amounts in the feces No metabolites of the vitamin have been identified Urinary excretion of the vitamin usually ranges from about 2 to 7 mg/day

15. Deficiency “Burning Feet Syndrome” Present in virtually ALL plant and animal foods, so a deficiency is highly unlikely Deficiency is thought to occur more often in conjunction with multiple nutrient deficiencies, for example malnutrition Syndrome can be corrected with calcium pantothenate administration

16. Deficiency Symptoms Characterized by: Numbness of toes and burning sensation in the feet Vomiting, fatigue, weakness, restlessness, and irritability Conditions that may increase the need for the vitamin Alcoholism DM Inflammatory bowel diseases

17. Toxicity Toxicity has not been reported to date in humans Intakes of about 10g pantothenate as calcium pantothenate daily for up to 6 weeks have resulted in no problems

18. Toxicity Symptoms Intakes of about 15 to 20g daily have been associated with: Mild intestinal distress Diarrhea

19. Food Sources The greek word pantos means “everywhere” Pantothenic acid is found widely distributed in nature Present in virtually ALL plant and animal foods Good sources: Meats (particularly liver), egg yolk, legumes, whole-grain cereals, potatoes, mushrooms, broccoli, and avocados Most adults consume about 4 to 7 mg pantothenic acid per day

20. Requirements The AI recommendation for adults age 19 years and older 5mg/day 6mg/day for pregnancy 7mg/day for lactation

21. Assessment Blood pantothenic acid concentrations <100 mg/dl reflects low dietary pantothenate intakes Urinary pantothenate excretion is considered to be a better indicator <1mg/day considered indicative of poor status

22. Recent Research High fat diets and pantothenic acid levels Pantothenic acid is heavily involved in fatty acid metabolism High fat diets have shown to affect liver CoA levels in rats A study was conducted in 2010 Purpose: to determine how a high fat diet affects Pantothenic acid metabolism

23. High Fat Diets and Pantothenic Acid Rats were fed either a 5% or 30% fat diet with limited amounts of pantothenic acid Ad libitum 28 days Urine Analysis was conducted on the last day

24. High Fat Diets and Pantothenic Acid Results Fat content of the diet affected pantothenic acid metabolism The plasma, liver, and adrenal pantothenic acid levels in the rats fed the 30% fat diet were significantly lower than with the 5% fat diet

25. High Fat Diets and Pantothenic Acid Discussion The high fat diet could inhibit Pantothenic acid absorption in the intestines The pantothenic acid is being used for fatty acid breakdown and synthesis An increased reliance on fat for fuel alters pantothenic acid metabolism

26. References Gropper, S., Smith, J., & Groff, J. (2009). Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth, Cengage Learning. Yoshida, E., Tsutomu, F., Ohtsubo, M., & Shibata, K. (2010). High fat diet lowers the nutritional status indicators of pantothenic acid in weaning rats. Biosci. Biotechno. Bichem., 74(8), 1691- 1693.